title: Ursolic and oleanolic acids as antimicrobial and immunomodulatory compounds for tuberculosis treatment.
abstract: BACKGROUND
  New alternatives for the treatment of Tuberculosis (TB) are urgently needed and medicinal plants represent a potential option. Chamaedora tepejilote and Lantana hispida are medicinal plants from Mexico and their hexanic extracts have shown antimycobacterial activity. Bioguided investigation of these extracts showed that the active compounds were ursolic acid (UA) and oleanolic acid (OA).
  
  
  METHODS
  The activity of UA and OA against Mycobacterium tuberculosis H37Rv, four monoresistant strains, and two drug-resistant clinical isolates were determined by MABA test. The intracellular activity of UA and OA against M. tuberculosis H37Rv and a MDR clinical isolate were evaluated in a macrophage cell line. Finally, the antitubercular activity of UA and OA was tested in BALB/c mice infected with M. tuberculosis H37Rv or a MDR strain, by determining pulmonary bacilli loads, tissue damage by automated histomorphometry, and expression of IFN-γ, TNF-α, and iNOS by quantitative RT-PCR.
  
  
  RESULTS
  The in vitro assay showed that the UA/OA mixture has synergistic activity. The intracellular activity of these compounds against M. tuberculosis H37Rv and a MDR clinical isolate in a macrophage cell line showed that both compounds, alone and in combination, were active against intracellular mycobacteria even at low doses. Moreover, when both compounds were used to treat BALB/c mice with TB induced by H37Rv or MDR bacilli, a significant reduction of bacterial loads and pneumonia were observed compared to the control. Interestingly, animals treated with UA and OA showed a higher expression of IFN-γ and TNF-α in their lungs, than control animals.
  
  
  CONCLUSIONS
  UA and OA showed antimicrobial activity plus an immune-stimulatory effect that permitted the control of experimental pulmonary TB.
authors.affiliation: Unidad de Investigación Médica en Farmacología, Hospital de Especialidades, CMN Siglo XXI, IMSS, Ave Cuauhtémoc 330, Col, Doctores, México 06720 D,F, México. adelinajim08@prodigy.net.mx.
authors.forename: Adelina
authors.initials: A
authors.lastname: Jiménez-Arellanes
authors.forename: Julieta
authors.initials: J
authors.lastname: Luna-Herrera
authors.forename: Jorge
authors.initials: J
authors.lastname: Cornejo-Garrido
authors.forename: Sonia
authors.initials: S
authors.lastname: López-García
authors.forename: María Eugenia
authors.initials: ME
authors.lastname: Castro-Mussot
authors.forename: Mariana
authors.initials: M
authors.lastname: Meckes-Fischer
authors.forename: Dulce
authors.initials: D
authors.lastname: Mata-Espinosa
authors.forename: Brenda
authors.initials: B
authors.lastname: Marquina
authors.forename: Javier
authors.initials: J
authors.lastname: Torres
authors.forename: Rogelio
authors.initials: R
authors.lastname: Hernández-Pando
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000995:Antitubercular Agents / Q000737:chemistry / Q000494:pharmacology*; D028023:Arecaceae / Q000737:chemistry; D058491:Bacterial Load / Q000187:drug effects; D015169:Colony Count, Microbial; D004357:Drug Synergism; D007155:Immunologic Factors / Q000737:chemistry / Q000494:pharmacology; D032410:Lantana / Q000737:chemistry; D008168:Lung / Q000187:drug effects / Q000382:microbiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D009828:Oleanolic Acid / Q000737:chemistry / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry*; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology*; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000382:microbiology; D000097245:Ursolic Acid
chemical_list: D000995:Antitubercular Agents; D007155:Immunologic Factors; D009828:Oleanolic Acid; D014315:Triterpenes; D000097245:Ursolic Acid